Heretofore, it is known that the fibroblast growth factor (FGF) ligand family comprises 22 members in humans and mice, and that each of these members has an inherent reaction specificity for one or more of seven FGF receptor (FGFR) subclasses, namely FGFR1c, FGFR1b, FGFR2c, FGFR2b, FGFR3c, FGFR3b and FGFR4. It is generally believed that the diversity of the physiological functions of FGF ligands is often explainable in terms of the combinations of various ligands and various receptors. On the other hand, few cases are known in which the inherent receptor specificities of the individual FGF ligands can be regulated artificially.
Under these circumstances, it has been reported that FGF18 can regulate the formation or growth of a bone or cartilage (Non-patent References Nos. 1 and 2). It has been also reported that FGF18 can induce the anagen phase of hair follicles to  stimulate the growth of hair (Non-patent Reference No. 3). However, it is not clear which of the FGF receptors binds and reacts with FGF18 to enable it to exhibit those and various other physiological activities of the FGF18. If the receptor specificity of naturally secreted FGF18 can be manipulated, then a factor which specifically exhibits or regulates any one of the various activities of FGF18 might be found. However, no such factors have been discovered yet. It is believed that naturally secreted FGF18 reacts with FGFR1c, FGFR2c, FGFR3c or FGFR4.
Heretofore, no mutant FGF18 proteins having different reaction specificities to FGF18 receptors have been known, and no mutant FGF18 proteins capable of regulating the activity of naturally secreted FGF18 have been known, either. Those mutant FGF18 proteins would be highly valuable, since FGF18 has an activity as a regulation factor for the hair growth, an activity as a regulation factor for the formation, growth or repairment of a bone or cartilage, and many other activities.    [Non-Patent Reference No. 1]    Ohbayashi N, Shibayama M, Kurotaki Y, Imanishi M, Fujimori T, Itch N, Takada S. FGF18 is required for normal cell proliferation and differentiation during osteogenesis and chondrogenesis. Genes Dev. 2002, 16(7):870-9    [Non-Patent Reference No. 2]    Moore E E, Bendele A M, Thompson D L, Littau A, Waggie K S, Reardon B, Ellsworth J L. Fibroblast growth factor-18 stimulates chondrogenesis and cartilage repair in a rat model of injury-induced osteoarthritis. Osteoarthritis Cartilage. 2005, 13(7):623-31     [Non-Patent Reference No. 3]    Kawano N, Komi-Kuramochi A, Asada M, Suzuki M, Oki J, Jiang J, Imamura T. Comprehensive analysis of FGF and FGFR expression in skin: FGF18 is highly expressed in hair follicles and capable of inducing anagen from telogen stage hair follicles. J Invest Dermatol. 2005, 124(5):877-885